A novel alternative to cryopreservation for the short-term storage of stem cells for use in cell therapy using alginate encapsulation

Efficient transport of stem/progenitor cells without affecting their survival and function is a key factor in any practical cell-based therapy. However, the current approach using liquid nitrogen for the transfer of stem cells requires a short delivery time window is technically challenging and financially expensive. The present study aims to use semipermeable alginate hydrogels (crosslinked by strontium) to encapsulate, store, and release stem cells, to replace the conventional cryopreservation method for the transport of therapeutic cells within world-wide distribution time frame. Human mesenchymal stem cell (hMSC) and mouse embryonic stem cells (mESCs) were successfully stored inside alginate hydrogels for 5 days under ambient conditions in an air-tight environment (sealed cryovial). Cell viability, of the cells extracted from alginate gel, gave 74% (mESC) and 80% (hMSC) survival rates, which compared favorably to cryopreservation. More importantly, the subsequent proliferation rate and detection of common stem cell markers (both in mRNA and protein level) from hMSCs and mESCs retrieved from alginate hydrogels were also comparable to (if not better than) results gained following cryopreservation. In conclusion, this new and simple application of alginate hydrogel encapsulation may offer a cheap and robust alternative to cryopreservation for the transport and storage of stem cells for both clinical and research purposes.

Enriching enterprise resource planning systems for strategic advantage: a semiotic motivated approach

Enterprise Resource Planning is often endorsed as a means to facilitate strategic advantage for businesses. The scarcity of resources is the method by which some businesses maintain their position. However, the ubiquitous trend towards the adoption of Enterprise Resourcing Planning systems coupled with market saturation makes the promise of advantage less compelling. Reported in this paper is a proposed solution based upon semiotic theory that takes a typical Enterprise Resource Planning deployment scenario and shapes it according to the needs of people in post-implementation contexts to leverage strategic advantage in different ways.

Constructing the frequency and wave normal distribution of whistler-mode wave power

We introduce a new methodology that allows the construction of wave frequency distributions due to growing incoherent whistler-mode waves in the magnetosphere. The technique combines the equations of geometric optics (i.e. raytracing) with the equation of transfer of radiation in an anisotropic lossy medium to obtain spectral energy density as a function of frequency and wavenormal angle. We describe the method in detail, and then demonstrate how it could be used in an idealised magnetosphere during quiet geomagnetic conditions. For a specific set of plasma conditions, we predict that the wave power peaks off the equator at ~15 degrees magnetic latitude. The new calculations predict that wave power as a function of frequency can be adequately described using a Gaussian function, but as a function of wavenormal angle, it more closely resembles a skew normal distribution. The technique described in this paper is the first known estimate of the parallel and oblique incoherent wave spectrum as a result of growing whistler-mode waves, and provides a means to incorporate self-consistent wave-particle interactions in a kinetic model of the magnetosphere over a large volume.

A spectral view of nonlinear fluxes and stationary-transient interaction in the atmosphere

Nonlinear spectral transfers of kinetic energy and enstrophy, and stationary-transient interaction, are studied using global FGGE data for January 1979. It is found that the spectral transfers arise primarily from a combination, in roughly equal measure, of pure transient and mixed stationary-transient interactions. The pure transient interactions are associated with a transient eddy field which is approximately locally homogeneous and isotropic, and they appear to be consistently understood within the context of two-dimensional homogeneous turbulence. Theory based on spatial wale separation concepts suggests that the mixed interactions may be understood physically, to a first approximation, as a process of shear-induced spectral transfer of transient enstrophy along lines of constant zonal wavenumber. This essentially conservative enstrophy transfer generally involves highly nonlocal stationary-transient energy conversions. The observational analysis demonstrates that the shear-induced transient enstrophy transfer is mainly associated with intermediate-scale (zonal wavenumber m > 3) transients and is primarily to smaller (meridional) scales, so that the transient flow acts as a source of stationary energy. In quantitative terms, this transient-eddy rectification corresponds to a forcing timescale in the stationary energy budget which is of the same order of magnitude as most estimates of the damping timescale in simple stationary-wave models (5 to 15 days). Moreover, the nonlinear interactions involved are highly nonlocal and cover a wide range of transient scales of motion.

The Copenhagen principles on the handling of detainees: implications for the procedural regulation of internment

The Copenhagen Principles on the Handling of Detainees in International Military Operations were released in October 2012 after a five-year long process involving states and certain organizations. The Principles address a number of issues concerning the handling and transfer of detainees. They apply in military operations conducted by states abroad in the context of non-international armed conflicts and peace operations. This article focuses on those principles that address the procedural regulation of internment (ie preventive, security detention), as it is here that the current law is particularly unclear. On the one hand, the treaty provisions applicable in non-international armed conflicts contain no rules on the procedural regulation of internment, in comparison with the law of international armed conflict. On the other hand, the relevant rules under international human rights law (IHRL) appear derogable in such situations. This article demonstrates that the approach taken to this issue in the Copenhagen Principles is one which essentially draws on the procedural rules applicable to civilian internment in the international armed conflicts. These rules adopt standards that are lower than those under IHRL. Reference is then made to other recent practice, which illustrates that the Copenhagen Principles do not apply in a legal vacuum. In particular, two recent judicial developments highlight the continued relevance of human rights law and domestic law, respectively, in regulating detention operations in the context of international military operations. Compliance with the Copenhagen Principles may not, therefore, be sufficient for detention to be lawful.

Antioxidant effects of ryegrass phenolics in lamb liver and plasma

Sixteen lambs were divided into two groups and fed two different diets. Eight lambs were stall-fed with a concentrate-based diet (C), and the remaining eight lambs were allowed to graze on Lolium perenne (G). The antioxidant status was measured in the liver and plasma samples before and after solid-phase extraction (SPE) to probe the antioxidant effects that grass phenolic compounds may have conferred onto the animal tissues. The liver and plasma samples from grass-fed lambs displayed a greater antioxidant capacity than the tissues from C lamb group, but only if samples had not been passed through SPE cartridges. Finally, the feed and animal tissues, which had been purified by SPE, were analysed by liquid chromatography combined with mass spectrometry (LC-MS) to identify phenolic compounds present in L. perenne and to evaluate the results from the antioxidant assays. It would appear that the improvement of the antioxidant capacity of lamb liver and plasma from lambs fed ryegrass was not related to the direct transfer of phenolic compounds from grass to the animal tissues.

Risk allocation in a public–private partnership: a case study of construction and operation of kindergartens in Kazakhstan

In Kazakhstan, a transitional nation in Central Asia, the development of public–private partnerships (PPPs) is at its early stage and increasingly of strategic importance. This case study investigates risk allocation in an ongoing project: the construction and operation of 11 kindergartens in the city of Karaganda in the concession form for 14 years. Drawing on a conceptual framework of effective risk allocation, the study identifies principal PPP risks, provides a critical assessment of how and in what way each partner bears a certain risk, highlights the reasons underpinning risk allocation decisions and delineates the lessons learned. The findings show that the government has effectively transferred most risks to the private sector partner, whilst both partners share the demand risk of childcare services and the project default risk. The strong elements of risk allocation include clear assignment of parties’ responsibilities, streamlined financing schemes and incentives to complete the main project phases on time. However, risk allocation has missed an opportunity to create incentives for service quality improvements and take advantage of economies of scale. The most controversial element of risk allocation, as the study finds, is a revenue stream that an operator is supposed to receive from the provision of services unrelated to childcare, as neither partner is able to mitigate this revenue risk. The article concludes that in the kindergartens’ PPP, the government has achieved almost complete transfer of risks to the private sector partner. However, the costs of transfer are extensive government financial outlays that seriously compromise the PPP value for money.

The rulB gene of plasmid pWW0 is a hotspot for the site-specific insertion of integron-like elements found in the chromosomes of environmental Pseudomonas fluorescens group bacteria

The rulAB operon of Pseudomonas spp. confers fitness traits on the host and has been suggested to be a hotspot for insertion of mobile elements that carry avirulence genes. Here, for the first time, we show that rulB on plasmid pWW0 is a hotspot for the active site-specific integration of related integron-like elements (ILEs) found in six environmental pseudomonads (strains FH1–FH6). Integration into rulB on pWW0 occurred at position 6488 generating a 3 bp direct repeat. ILEs from FH1 and FH5 were 9403 bp in length and contained eight open reading frames (ORFs), while the ILE from FH4 was 16 233 bp in length and contained 16 ORFs. In all three ILEs, the first 5.1 kb (containing ORFs 1–4) were structurally conserved and contained three predicted site-specific recombinases/integrases and a tetR homologue. Downstream of these resided ORFs of the ‘variable side’ with structural and sequence similarity to those encoding survival traits on the fitness enhancing plasmid pGRT1 (ILEFH1 and ILEFH5) and the NR-II virulence region of genomic island PAGI-5 (ILEFH4). Collectively, these ILEs share features with the previously described type III protein secretion system effector ILEs and are considered important to host survival and transfer of fitness enhancing and (a)virulence genes between bacteria.

Sequence analysis of a CTX-M-1 IncI1 plasmid found in Salmonella enterica 4,5,12,i:-, Escherichia coli and Klebsiella pneumoniae on a single UK pig farm

OBJECTIVES: In 2009, CTX-M Enterobacteriaceae and Salmonella isolates were recovered from a UK pig farm, prompting studies into the dissemination of the resistance and to establish any relationships between the isolates. METHODS: PFGE was used to elucidate clonal relationships between isolates whilst plasmid profiling, restriction analysis, sequencing and PCR were used to characterize the CTX-M-harbouring plasmids. RESULTS: Escherichia coli, Klebsiella pneumoniae and Salmonella 4,5,12:i:- and Bovismorbificans resistant to cefotaxime (n = 65) were recovered and 63 were shown by PCR to harbour a group 1 CTX-M gene. The harbouring hosts were diverse, but the group 1 CTX-M plasmids were common. Three sequenced CTX-M plasmids from E. coli, K. pneumoniae and Salmonella enterica serotype 4,5,12:i:- were identical except for seven mutations and highly similar to IncI1 plasmid ColIb-P9. Two antimicrobial resistance regions were identified: one inserted upstream of yacABC harbouring ISCR2 transposases, sul2 and floR; and the other inserted within shfB of the pilV shufflon harbouring the ISEcp1 transposase followed by blaCTX-M-1. CONCLUSIONS: These data suggest that an ST108 IncI1 plasmid encoding a blaCTX-M-1 gene had disseminated across multiple genera on this farm, an example of horizontal gene transfer of the blaCTX-M-1 gene.

The history of entrepreneurship: Medieval origins of a modern phenomenon

The origins of enterprise are often associated with the Industrial Revolution, but this article presents evidence of entrepreneurial activities from a much earlier date – the medieval period. Between 1250 and 1500 the church, merchants and members of the royal court all engaged in activities that demonstrated the entrepreneurial characteristics of innovation, risk-taking and judgement. The activities of the prior of Tynemouth and the career of the wool merchant William de la Pole illustrate these developments. By focusing on individuals rather than firms, it is possible to push back the study of entrepreneurship beyond the Industrial Revolution and early-modern trade to a period that witnessed the origins of the modern state.

The role of rules-based compliance systems in the new EU regulatory landscape: perspectives of institutional change

Purpose The research objective of this study is to understand how institutional changes to the EU regulatory landscape may affect corresponding institutionalized operational practices within financial organizations. Design/methodology/approach The study adopts an Investment Management System as its case and investigates different implementations of this system within eight financial organizations, predominantly focused on investment banking and asset management activities within capital markets. At the systems vendor site, senior systems consultants and client relationship managers were interviewed. Within the financial organizations, compliance, risk and systems experts were interviewed. Findings The study empirically tests modes of institutional change. Displacement and Layering were found to be the most prevalent modes. However, the study highlights how the outcomes of Displacement and Drift may be similar in effect as both modes may cause compliance gaps. The research highlights how changes in regulations may create gaps in systems and processes which, in the short term, need to be plugged by manual processes. Practical implications Vendors abilities to manage institutional change caused by Drift, Displacement, Layering and Conversion and their ability to efficiently and quickly translate institutional variables into structured systems has the power to ease the pain and cost of compliance as well as reducing the risk of breeches by reducing the need for interim manual systems. Originality/value The study makes a contribution by applying recent theoretical concepts of institutional change to the topic of regulatory change uses this analysis to provide insight into the effects of this new environment

Salt forms of Amides: protonation and polymorphism of Carbamazepine and Cytenamide

In situ generation of HCl or HBr in alcohol leads to O-protonation of the amide group of carbamazepine. Six salt phases have been produced using this method and their crystal structures determined by single crystal diffraction. A new polymorph of carbamazepine hydrochloride is described as are two polymorphs of carbamazepine hydrobromide. All are protonated at the amide O atom to give RC(OH)NH2 cations. Prolonged exposure to air results in addition of water to the solid salt forms. Such hydration of carbamazepine hydrobromide simply gives a monohydrated phase, but similar treatment of the equivalent hydrochloride results in partial loss of HCl and the transfer of the remaining proton from the amide group to water to give [carbamazepine][H3O]0.5[Cl]0.5·H2O. A similar hydronium chloride species is the only product isolated after reaction of the carbamazepine analogue cytenamide with HCl generated in methanol.

Cognitive and environmental factors influencing the process of spatial knowledge acquisition within virtual reality environments

As the fidelity of virtual environments (VE) continues to increase, the possibility of using them as training platforms is becoming increasingly realistic for a variety of application domains, including military and emergency personnel training. In the past, there was much debate on whether the acquisition and subsequent transfer of spatial knowledge from VEs to the real world is possible, or whether the differences in medium during training would essentially be an obstacle to truly learning geometric space. In this paper, the authors present various cognitive and environmental factors that not only contribute to this process, but also interact with each other to a certain degree, leading to a variable exposure time requirement in order for the process of spatial knowledge acquisition (SKA) to occur. The cognitive factors that the authors discuss include a variety of individual user differences such as: knowledge and experience; cognitive gender differences; aptitude and spatial orientation skill; and finally, cognitive styles. Environmental factors discussed include: Size, Spatial layout complexity and landmark distribution. It may seem obvious that since every individual's brain is unique - not only through experience, but also through genetic predisposition that a one size fits all approach to training would be illogical. Furthermore, considering that various cognitive differences may further emerge when a certain stimulus is present (e.g. complex environmental space), it would make even more sense to understand how these factors can impact spatial memory, and to try to adapt the training session by providing visual/auditory cues as well as by changing the exposure time requirements for each individual. The impact of this research domain is important to VE training in general, however within service and military domains, guaranteeing appropriate spatial training is critical in order to ensure that disorientation does not occur in a life or death scenario.

The effect of model configuration on modelled hillslope–riparian interactions

The transfer of hillslope water to and through the riparian zone forms a research area of importance in hydrological investigations. Numerical modelling schemes offer a way to visualise and quantify first-order controls on catchment runoff response and mixing. We use a two-dimensional Finite Element model to assess the link between model setup decisions (e.g. zero-flux boundary definitions, soil algorithm choice) and the consequential hydrological process behaviour. A detailed understanding of the consequences of model configuration is required in order to produce reliable estimates of state variables. We demonstrate that model configuration decisions can determine effectively the presence or absence of particular hillslope flow processes and, the magnitude and direction of flux at the hillslope–riparian interface. If these consequences are not fully explored for any given scheme and application, the resulting process inference may well be misleading.

The interconnection of the magnetic fields of the Earth and the sun

Magnetic reconnection facilitates the transfer of mass, energy, and momentum from the solar wind, through the Earth's magnetosphere and into the upper atmosphere. Recently, combined observations using both ground-based and satellite instruments have revealed much about how reconnection takes place. This new understanding has great signficance for systems which exploit, or operate within, the Earth's plasma environment, as well as for a wide variety of scientific studies.